Neisseria meningitidis (meningococcus) is a Gram negative strictly human pathogen and represents an important cause of morbiditiy and mortality worldwide. It colonizes the nasopharynx and in a small proportion of infected individuals, crosses the mucosal barrier, invades the bloodstream, causing fulminating septicemia or crosses the blood-brain barrier, resulting in meningitis. Within these niches, meningococcus is exposed to different environmental conditions and bacteria sense and respond to changes within or between niches through co-ordinated regulatory networks that alter protein and gene expression patterns. A multicomponent vaccine has been recently developed which protects against serogroup B meningococcus and the three main antigens, Neisserial heparin-binding antigen (NHBA), factor H-binding protein (fHbp) and Neisseria meningitidis adhesin A (NadA), have been implicated as playing important roles in meningococcal virulence. Our studies have focused on the regulatory mechanisms controlling the expression of these antigens as well as an understanding of the transcriptional and small regulatory RNA networks in meningococcus. Understanding the expression and molecular mechanisms of regulation of vaccine antigens and virulence factors is paramount to understanding their contribution towards protection against the pathogen as well as the infection process.